Prevention of hospitalization has long been viewed as a major health benefit of the use of influenza vaccine. This was, in large part, the rationale for the initial vaccination programs targeting the elderly and those with underlying health conditions. However, in the last decade, questions have been raised about the value of such programs. Modern study designs to assess vaccine effectiveness (VE) have required laboratory confirmation of influenza infection, as well as documentation of vaccine receipt and the use of a test-negative design to control for differences in healthcare-seeking behavior between vaccinated and unvaccinated patients. There is a need for current estimates of VE in preventing influenza-associated hospitalization using these methods. We propose estimation of influenza vaccine effectiveness in preventing influenza hospitalization in two health systems in Michigan, where we have been conducting annual assessments of VE in various populations since 2008. We will conduct surveillance at two hospitals, and will enroll adult in-patients with acute respiratory infection. Vaccination status will be reported and documented, and considered with laboratory-confirmed influenza outcomes to estimate vaccine effectiveness for prevention of hospitalization. Analyses will use a test- negative design; those testing positive for influenza ar cases, those testing negative are controls. Modifiers and confounders of vaccine effectiveness such as age, health status, high-risk health conditions, functional status, frailty, education, tim from illness onset to specimen collection, calendar time, and propensity for vaccination will be assessed. In addition to our proposed influenza surveillance and VE assessment, we propose an estimation of the incidence of hospitalization in adults due to respiratory syncytial virus (RSV and other respiratory viruses. This will allow for the evaluation of bias in influenza VE assessment due to interaction between influenza vaccination, infection, and non-influenza respiratory viruses, and will establish a platform for the future evaluation of RSV vaccines. We will accomplish these additional objectives by expanding our surveillance to months before and after the typical influenza season and evaluating specimens by molecular methods for RSV and other respiratory viruses.